Inner retinal hyper-reflective foci number correlates with flood-illumination adaptive optics ophthalmoscopy grading and systemic organ involvement in patients with Fabry disease

Objectives: To determine the correlation of inner retinal hyper-reflective foci (HRFs) number with Flood-illumination Adaptive Optics Ophthalmoscopy (FIAOO) grading and systemic organ involvement in a cohort of patients with Fabry disease (FD). Methods: Observational and cross-sectional study. Thirty-two eyes of 16 genetically proven FD patients (11 females) were included in the analysis. Data regarding therapeutic regimen and organ involvement (heart, kidney, and brain) of each patient were reviewed. Patients underwent full ophthalmological examination including best-corrected visual acuity, retinography, spectral domain optical coherence tomography and FIAOO imaging grading of retinal vessels. The number of inner-retinal HRFs was determined within the central 2500 μm at the foveal level in each patient and correlation with ocular imaging findings and systemic involvement parameters was assessed through Spearman correlation analysis and Generalized Linear Models (GLM) with a robust Huber White standard error estimation. Results: Inner retinal HRFs number showed a significant association with male gender, use of enzyme replacement therapy and presence of retinal vessel tortuosity (all p < 0.001). Severity of NHYA class and presence of cornea verticillata reached a quasi-significant association (p = 0.089 and p = 0.07, respectively). Increase of FIAOO grading was associated to increased HRFs number (p < 0.001) and increase in estimated glomerular filtration rate was inversely associated with HRFs number (p = 0.04). Conclusions: Inner retinal HRF number correlated with organ involvement and ocular imaging findings in FD patients. They may represent a biomarker of disease severity in diagnosed patients and their presence should enhance the suspect of FD in the appropriate clinical setting.